Melanogenesis is the scientific term to refer to skin pigmentation. Although melanogenesis is necessary as a mechanism of defense against UV radiation, a disruption of this process may cause an abnormal accumulation of melanin called hyperpigmentation, including melisma and senile lentigines.
The evolution of the melanogenesis pathway takes place in the epidermis, in particular in dendritic cells, which interact with keratinocytes: melanocytes. These latter contain specific organelles called melanosomes: site of the synthesis of different pigments (melanins), responsible for our specific skin color, i.e. phototype.
Among black people, hyperpigmentation is visualized by a spotted and uneven skin. It may be the result of immune system activity in response to inflammation, infection and/or healing but also of daily use of topical products containing substances lightening, now banned in cosmetics, such as hydroquinone and/or topical corticosteroids.
In order to reduce these dermatoses, understanding the mechanisms of melanogenesis is essential. Thus, it will be easier to visualize where the potential inhibitor will act to stop and/or reduce its production of melanin.
The melanogenic pathway is a complex process that allows the production of two different skin pigments: black-brown eumelanins and yellow to reddish pheomelanins. Tyrosinase is the key enzyme required for melanin production. Her first function is the hydroxylation of tyrosine to dihydroxyphenylalanine (DOPA), the rate-limiting step of this process. Tyrosinase allows the oxidation of DOPA to DOPAquinone. Then, two pathways can be chosen.
In the absence of thiol compounds (cysteine) (Black population), DOPAquinone is oxidized spontaneously to dopachrome, a red intermediate product. This latter can cyclize spontaneously to give 5,6-dihydroxyindole (DHI), a black insoluble molecule, or be converted into 5,6-dihydroxyindole-2-carboxylic-acid (DHICA) in the presence of a second enzyme: Tyrosinase-Related-Protein 2 (TRP-2). This second intermediate must be in the presence of a DHICA oxidase activity to be converted into DHICA-melanins. This activity is ported by Tyrosinase-Related-Protein 1 (TRP-1).
Using skin bleaching cosmetics has been a social practice for about 30 years in the black female population. Today, this concept is spreading on men in certain countries in central Africa. Currently, 60% of black African women admit to use skin lightening products in order to obtain a clearer and more uniform complexion. This practice, initiated by the media, may not only cause significant dermatological complications but also systemic complications in the long run. About 70% of users have skin problems such as keloid acne, trophic disorders, hyperpigmentation, etc. These further complications, foremost dermatologic in the first time, come from the toxic activity of the compounds present in lightener products such as hydroquinone or mercury derivatives.
Currently, in France and in Africa, the most active substances used are hydroquinone, often at high concentrations exceeding 4% and topical corticosteroids with strong activity, such as clobetasol propionate at 0.05%, which is one of the most potent topical corticosteroids. These products are used in the form of creams (hydroquinone or steroids), gels (corticosteroids) or milk (hydroquinone). The amount of active substance is often indicated but may be imprecise. The use of mercuray derivatives, previously widespread seems to be more limited today. They may be used in the form of soaps called “antiseptic”.
A prospective, descriptive study has been performed over a 6-month period in Senegal including 86 female patients with a mean age of 29-34 years-old (range 16-49 years-old). The break-down by skin-bleaching products showed that topical corticosteroids were the most frequently used (78%), followed by hydroquinone (56%), products based on vegetable extracts (31.7%), caustic products (8.5%) and finally, products of unknown composition (41.4%). Two components or more are frequently combined (86.5%).
Of the 19 types of complications listed, dyschromia, including hyperpigmentation of the joints, was clearly the most common. This remains a significant stigma associated with artificial depigmentation, with 85.4% sensitivity. Striae atrophicae (72%) and skin atrophy (52.4%) were also very common, testifying to the very frequent use of corticosteroids.
Moreover, since several years, evidences demonstrating that there are links between the production of reactive oxygen species (ROS) and melanin overproduction have been well described in the literature. Indeed, UV stimulation induces melanin production which in turn provokes ROS or H2O2 release in the skin leading to skin aging. Some flavonoid compounds are also known for their properties able to both inhibit melanin and ROS production (For review: GILLBRO & OLSSON, Int. J. Cosmet. Sci., vol. 33(3):210-21, 2011) Thus, the identification of tyrosinase or TRP-1 inhibitors may have an interest for treating skin aging.
Thus, there remains a need in the art for substances and cosmetic compositions able to regulate the melanogenesis pathway without side effect for black and mixed skin (phototype IV-VI).